ObjectiveTo explore the effect of elbow-wrist functional orthosis on plantar pressure distribution and balance function in stroke patients with hemiplegia. MethodsFrom June, 2024 to April, 2025, 60 patients with post-stroke hemiplegia were recruited from Huashan Hospital, Fudan University, and Shanghai Hebin Rehabilitation Hospital. They were randomly divided into control group (n = 30) and intervention group (n = 30). The control group received routine neurological rehabilitation, while the intervention group received additional training with an elbow-wrist functional orthosis on the affected side, for eight weeks. Before and after intervention, the Modified Ashworth Scale (MAS) of the elbow joint, plantar pressure symmetry index (SI), plantar contact area and mean plantar pressure were recorded, and balance and mobility were assessed using the Berg Balance Scale (BBS), Timed Up & Go Test (TUGT) and 10-Meter Walk Test (10MWT). ResultsTwo cases dropped out in the control group. After treatment, MAS grades of the elbow joint, forefoot SI, affected side plantar pressure area, BBS scores, TUGT and 10MWT of both groups improved (|Z| > 3.969, |t| > 3.528, P < 0.01), while the hindfoot SI and average pressure of the affected foot improved in the intervention group (∣t∣ > 4.264, P < 0.001). Except for TUGT and 10MWT, the intervention group was superior to the control group (∣Z∣ > 2.030, ∣t∣ > 2.096, P < 0.05). ConclusionThe elbow-wrist functional orthosis can enhance balance function in stroke patients with hemiplegia by reducing upper-limb spasticity, optimizing center-of-gravity distribution, and improving postural control.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

ObjectiveTo investigate the clinical features and traditional Chinese medicine （TCM） syndrome distribution of treatment-naïve patients with hepatitis B virus-related primary liver cancer （HBV-PLC）， and to provide a basis for integrated traditional Chinese and Western medicine in the prevention and treatment of HBV-PLC. MethodsA retrospective analysis was performed for the clinical data of 99 treatment-naïve HBV-PLC patients who were admitted to Department of Hepatology and Infectious Diseases in The First Affiliated Hospital of Hunan University of Chinese Medicine from January 2019 to December 2024. According to whether the patient received standardized antiviral therapy （for ≥3 years）， they were divided into antiviral group and non-antiviral group， and according to the status of HBeAg， they were divided into HBeAg-positive group and HBeAg-negative group. Demographic features， laboratory test results， imaging data， and TCM syndrome data were collected， and neutrophil-to-lymphocyte ratio （NLR）， Child-Pugh score， and CNLC stage were calculated. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. ResultsThe 99 treatment-naïve HBV-PLC patients had a mean age of 57.12±11.60 years， and the patients aged 50 — 75 years accounted for the highest proportion of 72.7%， with a male/female ratio of 5.2∶1. The patients with liver cirrhosis accounted for 81.8%， and 67.7% of the patients did not receive antiviral therapy in the past. The positive rates of HBV DNA， HBeAg， and alpha-fetoprotein were 80.8%， 18.2%， and 69.7%， respectively， and the patients with Child-Pugh class A/B disease accounted for 89.9%. Compared with the non-antiviral group， the antiviral group had a significantly smaller maximum tumor diameter （t=2.310， P=0.024）， a significantly lower HBV DNA positive rate （χ²=14.006， P<0.001）， and a significantly lower number of tumor thrombi （χ²=7.347， P=0.007）. In addition， there were significant differences between the HBeAg-negative group and the HBeAg-positive group in Child-Pugh class （χ²=6.780， P=0.034） and CNLC stage （χ²=8.746， P=0.033）. Among the 99 treatment-naïve HBV-PLC patients， 41.4% had liver depression and spleen deficiency with blood stasis， 22.2% had Qi deficiency and blood stasis syndrome， and 19.2% had damp-heat accumulation with blood stasis. ConclusionTreatment-naïve HBV-PLC patients are mainly middle-aged and elderly male individuals， and most of the patients are comorbid with liver cirrhosis. Standardized antiviral therapy can significantly reduce tumor burden and improve virologic response， with better hepatic compensation in HBeAg-negative patients， and hypoproteinemia is more common in patients with Qi deficiency and blood stasis syndrome.

In the traditional theoretical system of traditional Chinese medicine， latent pathogenic factors deeply hiding in the liver and gallbladder of the Jueyin meridian are the core pathogenesis of chronic hepatitis B. Interferon can regulate immunity and eliminate viruses， and clinical cure can be achieved by penetrating and removing pathogenic factors and toxins. However， it often causes dizziness and confusion reactions in the initial stage of treatment， and long-term use can damage Qi-blood； furthermore， its therapeutic effect depends on the patient’s own vital Qi. When traditional Chinese medicine is used in combination with interferon， drug compatibility should be adjusted according to the dynamic changes of pathogenesis， which can reduce adverse reactions， enhance the therapeutic outcome， expand the applicable population of interferon， and improve the clinical symptoms of patients.

Objective:To screen out the differentially expressed genes(DEGs)in multiple primary lung cancers(MPLCs)using bioinformatics methods,and to analyze their biological functions and their influence in the prognosis of lung adenocarcinoma.Methods:Single-cell transcriptome sequencing data(GSE200972)was downloaded from the Gene Expression Omnibus(GEO)database.After preliminary data processing with R software,the Seurat R package was used for data processing,cell clustering,and annotation.The clusterProfiler R package was used for Gene Set Enrichment Analysis(GSEA).The STRING database and Cytoscape software were employed to construct the protein-protein interaction(PPI)network and to screen out the key genes(Hub genes).The gene expression levels in the lung adenocarcinoma database were analyzed using Gene Expression Profiling Interactive Analysis(GEPIA)database.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the gene expression in tumor tissue of A549 xenograft mice and lung tissue of normal mice.Kaplan-Meier Plotter was used for prognosis analysis.Results:Seven cell types were identified from cell clustering analysis,which were epithelial cells,endothelial cells,fibroblasts,T cells and natural killer(NK)cells,B cells,myeloid cells,and mast cells.A total of 14 605 DEGs were screened out between tumor epithelial cells and normal epithelial cells.The GSEA results revealed four activated pathways in tumor samples[myelocytomatosis oncogene(MYC)pathway,P53 pathway,oxidative phosphorylation pathway and glycolysis pathway]and one inhibited pathway[tumor necrosis factor-α(TNF-α)and nuclear factor kappa B(NF-κB)pathway].The Hub genes identified from PPI network included CXC motif chemokine ligand 8(CXCL8),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),CXC motif chemokine receptor 4(CXCR4),kirsten rat sarcoma viral proto-oncogene(KRAS),CXC motif chemokine ligand 1(CXCL1),C-C motif chemokine ligand 2(CCL2),mucin 1(MUC1),and secreted phosphoprotein 1(SPP1).The GEPIA database analysis and animal experiments showed that the expression levels of SPP1 mRNA in non-small cell lung cancer tissue were increased compared with normal lung tissue(P＜0.01).The Kaplan-Meier survival analysis indicated that the patients with high expression level of SPP1 had shorter overall survival(OS)than those with low expression level(P＜0.01).Conclusion:There are activation of oncogene-related pathways and activation of tumor suppressor pathway antagonizing tumor progression in MPLCs.Moreover,elevated expression of SPP1 in non-small cell lung cancer may indicate a relatively poor prognosis.

OBJECTIVE: This review summarized the first 10-year progresses and controversies in the concept of anteromedial cortical support reduction, to provide references for further study and clinical applications. METHODS: Relevant domestic and foreign literature on cortical support reduction was extensively reviewed to summarize the definition of positive, neutral, and negative support, anteromedial cortices at the inferior corner, intraoperative technical tips for fracture reduction, radiographic assessment at different periods, comparison between positive versus neutral and medial versus anterior support, and the clinical efficacy of Chang reduction quality criteria (CRQC) and postoperative stability score. RESULTS: Anteromedial cortical support reduction was only focused on the cortex of anteromedial inferior corner, with no concern the status of lateral wall or lesser trochanter. Anteromedial cortex was seldom involved by fracture comminution, it was thicker, denser, and stronger, and was the key for mechanical buttress of the head-neck fragment to share compression load. Positive, neutral, and negative support were also called "extramedullary, anatomic, and intramedullary reduction", respectively. There was hardly seen parallel cortical apposition, but characterized by some kinds of head-neck rotation, for example 10°-15° flexed rotation for positive cortical contact and support. Due to intraoperative compression and postoperative impaction, the status of cortical support may be changed at different time of radiographic examination. The positive medial cortex support was more reliable with less reduction loss than its neutral counterpart, and the anterior cortex contact was more predictive than the medial cortex for final results. As incorporation the bearing of cortex apposition and using a 4-point score, CRQC demonstrated more efficacy and was gradually accepted and applied in the evaluation of trochanteric fracture reduction quality. Postoperative stability score (8 points) provided a assessment tool for early weight-bearing in safety to prevent mechanical failure. CONCLUSION Anteromedial cortical support reduction is a key point for stability reconstruction in the treatment of trochanteric femur fractures. Evidence has definitely shown that non-negative (positive and neutral) is superior to negative (loss of cortical support). There is a tendency that positive cortex support is superior to neutral, but high quality study with large sample size is needed for a clear conclusion.
Humans ; Femur/diagnostic imaging* ; Fracture Fixation, Internal/methods* ; Hip Fractures/diagnostic imaging* ; Treatment Outcome ; Fracture Fixation, Intramedullary/methods*

OBJECTIVE To observe the clinical efficacy of Zhenshi Burn Ointment on postoperative wound healing of simple anal fistula and explore its potential mechanism of action.METHODS A total of 60 patients with low-position simple anal fistula of damp-heat pouring downward type admitted to the Department of Anorectum,Nanjing Hospital of Chinese Medicine Affiliated to Nan-jing University of Chinese Medicine from May to December 2023 were selected as the research subjects and randomly divided into an experimental group and a control group,with 30 cases in each group.After surgery,the control group was given sterilized vaseline gauze for external application,and the experimental group was given Zhenshi Burn Ointment for external application.The course of treatment for both groups was 30 d.After treatment,the postoperative wound healing time,wound healing rate,pain score,wound granulation growth and secretion,and changes in TCM syndrome score were compared between the two groups.The pathological sec-tions of wound granulation tissue were compared 14 d after surgery.The transcription levels of COL1A1,type Ⅲ collagen(COL3A1),epidermal growth factor(EGF),and fibroblast growth factor(FGF2)in granulation tissue were detected by qPCR.The expression lev-els of proteins related to MEK/ERK signaling pathway were detected by Western blot.RESULTS Compared with the control group,the wound healing rates of the experimental group were significantly increased at 7,14,21,and 30 d after surgery(P<0.01),and the wound healing time was significantly shortened(P<0.01).At 7 d after surgery,the pain score of the experimental group was signifi-cantly lower than that of the control group(P<0.05).At 7 and 14 d after surgery,the granulation growth score of the wound in the ex-perimental group was significantly lower than that of the control group(P<0.01).At 14 d after surgery,the secretion score of the ex-perimental group was significantly lower than that of the control group(P<0.01).At 14 and 30 d after surgery,the total score of TCM syndrome in the experimental group was significantly better than that in the control group(P<0.05).At 14 d after surgery,the patho-logical improvement of granulation tissue in the wound in the experimental group was better than that in the control group,and the con-tent of collagen fiber and type I collagen(Collagen I)was significantly higher than that in the control group(P<0.01).The mRNA contents of COL1A1,COL3A1,EGF,and FGF2 were significantly higher than those in the control group(P<0.05,P<0.01);the levels of p-MEK1/2 and p-ERK1/2 proteins were higher than those in the control group(P<0.05).CONCLUSION Zhenshi Burn Ointment has a good effect on promoting postoperative anal fistula wound healing,which may be related to upregulating growth factor expression,promoting collagen regeneration,and activating MEK/ERK pathway.

Intraoperative neural monitoring (IONM) combines electrophysiology with anatomy to monitor nerve function during thyroid surgery,and has become an important auxiliary technology for neuroprotection. After more than ten years of development,the technology has been widely applied and popularized in China,promoting the development of a number of new technologies in the industry. Combined with the questionnaire survey data of the Chinese Neural Monitoring Study Group,this paper aims to summarize the clinical effect of IONM technology, the application status and existing problems at home and abroad, and propose the possible future development direction.

Tertiary lymphoid structures (TLSs), as a crucial component of the tumor micro-environment, have attracted significant attention in the field of tumor research in recent years. TLSs are composed of multiple immune cells and formed under the stimulation of chronic inflammation, with their maturation process divided into different stages. They exert anti-tumor effects by mimic-king the functions of secondary lymphoid organs and generating adaptive immune responses. In terms of the prognosis of gastric cancer, the cell composition, spatial distribution of TLSs, and their combination with other indicators are all helpful in predicting the prognosis of patients. Meanwhile, the TLSs scoring system is expected to become an index for evaluating the efficacy of immuno-therapy. Treatment strategies for inducing TLSs formation have achieved certain results in animal models, but potential treatment risks require attention. The authors elaborate on formation and maturation process of TLSs, anti-tumor mechanism, value in prognostic assessment of gastric cancer and multiple tumors, prediction of immunotherapy, as well as treatment strategies for inducing the formation of TLSs.